The invention relates to the use of a novel seventeen amino acid peptide to treat cerebral ischemia and ischemic heart disease including reperfusion injury.
Tissues deprived of blood and oxygen undergo ischemic necrosis or infarction with possible irreversible organ damage. Cerebral ischemia results from decreased blood and oxygen flow implicating one or more of the blood vessels of the brain. In cerebral ischemia, the individual suffers a stroke with sudden development of a focal neurologic deficit and, in most cases, some degree of brain damage. The decreased blood flow may be due to, for example, an occlusion such as a thrombus or embolus, vessel rupture, sudden fall in blood pressure, change in the vessel lumen diameter due to atherosclerosis, trauma, aneurysm, developmental malformation, altered permeability of the vessel wall or increased viscosity or other quality of the blood. Decreased blood flow may also be due to failure of the systemic circulation and severe prolonged hypotension. Ischemic necrosis of the spinal cord may result in sensory or motor symptoms or both that can be referred to cervical, thoracic or lumbar levels of the spine. Ischemic heart disease results from an imbalance between myocardial oxygen supply and demand. In ischemic heart disease, the individual suffers angina pectoris, acute myocardial infarction or sudden death. The imbalance may be caused by, for example, atherosclerotic obstruction of one or more large coronary arteries, nonatheromatous coronary obstructive lesions such as embolism, coronary ostial stenosis associated with luetic aortitis, coronary artery spasm, congenital abnormalities of the coronary circulation, increased myocardial oxygen demands exceeding the normal supply capabilities as in severe myocardial hypertrophy, reduction in the oxygen carrying capacity of the blood such as n anemia, or as a consequence of inadequate cardiac perfusion pressure due to hypotension from any cause. U.S. Pat. No. 6,294,579 B1 discloses methods for treating ischemia by administering certain Deltorphin peptides. The publication by Lazarus et al., xe2x80x9cEnvironmental Health Perspectivesxe2x80x9d, Vol. 102, No. 4, pages 648-654 (1994), discloses naturally occurring opiod peptides.
Current treatments for ischemia encompass behavioral changes drug therapy, and/or surgical intervention. Drugs are frequently preferred before resorting to invasive procedures and to provide more immediate relief than long-term behavioral changes. Thus, there is a need for a therapeutic agent which can be useful in treating or preventing ischemia.
It is an object of the invention to provide a novel peptide and use of that peptide to treat ischemia.
The present invention meets the object by providing a novel seventeen amino acid peptide (Peptide P) which is useful for treating cerebral ischemia and ischemic heart disease. Also provided is a method of treating ischemia in a mammal comprised administering a pharmaceutically effective amount of Peptide P tc said mammal. The ischemic tissue may be brain, spinal cord or heart.
The present invention is also directed to a method of reducing the effect of an ischemic episode comprised of administering an effective amount of pharmaceutically effective amount of Peptide P to said mammal.
The present invention is also directed to a method of treating cerebral or spinal cord ischemia or ischemic heart disease in a mammal comprised of administering an effective amount of pharmaceutically effective amount of Peptide P to said mammal.
Preferably, Peptide P is administered as a pharmaceutical composition at a dosage in the range of about 0.5 mg/kg body weight to about 20 mg/kg body weight, or alternatively lower doses in the range of about 1 mg/kg body weight to about 1000 mg/kg body weight of the mammal. Preferably, the mammal is human.